{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,14]],"date-time":"2026-03-14T01:11:47Z","timestamp":1773450707059,"version":"3.50.1"},"reference-count":85,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,9,7]],"date-time":"2021-09-07T00:00:00Z","timestamp":1630972800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell Dev. Biol."],"abstract":"<jats:p>Significantly reduced levels of the anti-inflammatory gaseous transmitter hydrogen sulfide (H<jats:sub>2<\/jats:sub>S) are observed in diabetic patients and correlate with microvascular dysfunction. H<jats:sub>2<\/jats:sub>S may protect the microvasculature by preventing loss of the endothelial glycocalyx. We tested the hypothesis that H<jats:sub>2<\/jats:sub>S could prevent or treat retinal microvascular endothelial dysfunction in diabetes. Bovine retinal endothelial cells (BRECs) were exposed to normal (NG, 5.5 mmol\/L) or high glucose (HG, 25 mmol\/L) \u00b1 the slow-release H<jats:sub>2<\/jats:sub>S donor NaGYY4137 <jats:italic>in vitro<\/jats:italic>. Glycocalyx coverage (stained with WGA-FITC) and calcein-labeled monocyte adherence were measured. <jats:italic>In vivo<\/jats:italic>, fundus fluorescein angiography (FFA) was performed in normal and streptozotocin-induced (STZ) diabetic rats. Animals received intraocular injection of NaGYY4137 (1 \u03bcM) or the mitochondrial-targeted H<jats:sub>2<\/jats:sub>S donor AP39 (100 nM) simultaneously with STZ (prevention) or on day 6 after STZ (treatment), and the ratio of interstitial to vascular fluorescence was used to estimate apparent permeability. NaGYY4137 prevented HG-induced loss of BREC glycocalyx, increased monocyte binding to BRECs (<jats:italic>p<\/jats:italic> \u2264 0.001), and increased overall glycocalyx coverage (<jats:italic>p<\/jats:italic> \u2264 0.001). In rats, the STZ-induced increase in apparent retinal vascular permeability (<jats:italic>p<\/jats:italic> \u2264 0.01) was significantly prevented by pre-treatment with NaGYY4137 and AP39 (<jats:italic>p<\/jats:italic> &amp;lt; 0.05) and stabilized by their post-STZ administration. NaGYY4137 also reduced the number of acellular capillaries (collagen IV + \/IB4-) in the diabetic retina in both groups (<jats:italic>p<\/jats:italic> \u2264 0.05). We conclude that NaGYY4137 and AP39 protected the retinal glycocalyx and endothelial permeability barrier from diabetes-associated loss of integrity and reduced the progression of diabetic retinopathy (DR). Hydrogen sulfide donors that target the glycocalyx may therefore be a therapeutic candidate for DR.<\/jats:p>","DOI":"10.3389\/fcell.2021.724905","type":"journal-article","created":{"date-parts":[[2021,9,7]],"date-time":"2021-09-07T05:34:02Z","timestamp":1630992842000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":11,"title":["Hydrogen Sulfide Is a Novel Protector of the Retinal Glycocalyx and Endothelial Permeability Barrier"],"prefix":"10.3389","volume":"9","author":[{"given":"Claire L.","family":"Allen","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katarzyna","family":"Wolanska","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Naseeb K.","family":"Malhi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew V.","family":"Benest","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark E.","family":"Wood","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Winfried","family":"Amoaku","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roberta","family":"Torregrossa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matthew","family":"Whiteman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David O.","family":"Bates","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jacqueline L.","family":"Whatmore","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2021,9,7]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1007\/s00281-008-0111-x","article-title":"Immunological mechanisms in the pathogenesis of diabetic retinopathy.","volume":"30","author":"Adamis","year":"2008","journal-title":"Semin. 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